Large, anovulatory follicles are a normal finding during the spring and fall transition periods. Anovulatory follicles can exceed 10 cm in diameter and may persist for several weeks. The cause is likely to be abnormal estrogen production by the follicle and/or insufficient release of pituitary gonadotropin to induce ovulation. Often the ultrasonographic image reveals scattered free-floating echogenic spots as a result of the presence of blood in the follicular fluid (hemorrhagic follicles). In others are echogenic fibrous bands resulting from gelatinization of the hemorrhagic fluid. Although human chorionic gonadotropin (2500 IU IV) or a GnRH implant may induce ovulation, in most cases the treatment is ineffective. Fortunately most of these anovulatory follicles spontaneously regress within 1 to 4 weeks. Breeding a mare in anticipation of ovulation of a persistent follicle is unwise because fertility of the aged oocyte is likely to be poor.
Clinicians should be aware that not all palpable and ultrasonographically imaged structures around the ovary have to be follicles. Fossa cysts and parovarian (fimbrial) cysts can be found in many mares as an incidental finding.
These structures tend to arise from remnants of the embryonic (mullerian and wolffian) duct systems. If they are of a significant size they should be noted on the mare’s breeding records, but they generally are not associated with any reduction in fertility. Theoretically an excessively large cyst could interfere with ovulation or oocyte transport.
During the physiologic breeding season in a healthy, non-pregnant mare, a surge of luteinizing hormone from the anterior pituitary results in rupture of the mature follicle (ovulation). Normally some hemorrhage from blood vessels in the theca layer occurs, and this results in a soft, intermediate structure — the corpus hemorrhagicum. Immediately after ovulation a depression may be palpable, but this is soon replaced by the developing corpus luteum. The theca cells and invading granulosa cells become luteinized such that the serum progesterone level is elevated until endometrial prostaglandin brings about luteolysis.
A hematoma is the most likely explanation for a unilateral ovarian enlargement during the physiologic breeding season. Excessive postovulatory hemorrhage is not uncommon. The former follicle can become distended markedly. Treatment is not indicated because the structure is essentially an abnormally large corpus hemorrhagicum. Behavior will be normal. The mare continues to have regular estrous cycles, and the opposite ovary remains functional. Serum hormone levels are normal. The hematoma resolves over a period of several weeks, and normal ovarian function can be expected to return in most cases.
Although an ovarian tumor could begin development during pregnancy, the most likely explanation for ovarian enlargement and abnormal behavior during this time is normal physiologic events. Secondary corpora lutea tend to cause bilateral ovarian enlargement after approximately day 40 of gestation. Expressions of estrus and stallion-like or just aggressive behavior can occur during pregnancy. The large fetal gonads are a significant source of testosterone. Obviously progesterone from the corpora lutea and progestins from the placenta are present. By 2 to 3 months of gestation, testosterone levels can exceed 100 pg/ml and then continue to rise until about 6K months. The testosterone concentrations then gradually decline to basal levels at parturition.
Granulosa Cell Tumors
In a normal ovary the granulosa cells line the inside of follicles, whereas the theca cells surround the outside of the follicle. The theca cells produce testosterone. Both the granulosa and theca cells are involved in the steroidogenic pathway that leads to estradiol production. The granulosa cells also produce the protein hormone, inhibin.
The granulosa cell tumor (GCT) is the most common tumor of the equine ovary. These tumors tend to be unilateral, slow growing, and benign. In fact, they can develop during pregnancy. If a GCT is detected at the foal heat, it may be possible to remove the ovary and have the mare bred back later that season. This depends on the time of year that the mare foals and also the degree of follicular suppression present in the contralateral ovary.
Although GCTs are steroidogenically active, the hormonal milieu can vary from case to case. This affects the amount of follicular activity on the contralateral ovary and the type of behavior being exhibited. Typically the opposite ovary is small and inactive, but occasionally a GCT presents on one ovary while a corpus luteum is on the other. Owners may report that the mare has failed to exhibit estrous behavior (prolonged anestrus) or that it is continuously displaying signs of being in estrus (nympho-mania). A dangerous side effect in some mares is aggressive behavior towards the handler. These mares tend to exhibit stallion-like behavior and may develop a crested neck and clitoral hypertrophy if the tumor has been present for some time.
Loss of the characteristic kidney-bean shape is usually a good indication that a tumor may be present in a small ovary (). Often the ovary is too large to be palpated thoroughly. In both instances the characteristic multicystic (honeycomb) image on an ultrasound examination can support the diagnosis (). Occasionally the GCT may present as a large unilocular cyst ().
The ultrasonographic diagnosis can be supported by hormonal assays if necessary (Table Hormonal Concentrations in Mares with a Granulosa Cell Tumor). Most GCT appear to secrete sufficient inhibin to suppress pituitary release of follicle-stimulating hormone (FSH), and this probably explains the typical suppression of follicular activity on the contralateral ovary. If a significant theca cell component exists in the tumor then the serum testosterone level is elevated, and these mares are more likely to be aggressive and exhibit stallion-like behavior. Although progesterone levels tend to be low (<1 ng/ml) in affected mares, in some instances cyclic activity may continue in the presence of a GCT.
Table Hormonal Concentrations in Mares with a Granulosa Cell Tumor
|Testosterone||More than 50 to 100 pg/ml||50%-60% of cases|
|Inhibin||More than 0.7 ng/ml||-90% of cases|
Indications for removal of these benign tumors include breeding purposes, behavioral problems, and in some cases colic episodes. Diagnosis must be certain because a histopathologic diagnosis of normal ovarian tissue can be difficult to explain to an owner once the ovary has been removed. Veterinarians must explain to owners that not all behavioral problems are ovarian in origin. An endometrial biopsy and cervical evaluation are recommended if the mare is to be used for breeding purposes. Although the abnormal hormonal environment can cause reversible changes in the density of the endometrial glands, chronic degenerative changes including fibrosis limit the mare’s ability to carry a foal to term. The affected ovary can be removed by several surgical approaches, depending on the size of the GCT and the preference of the surgeon. Options for ovariectomy include laparoscopy, colpotomy, and flank and ventral midline laparotomy. The time until subsequent ovulation on the remaining ovary can vary tremendously, and owners should be advised that it might take up to 6 to 8 months.
Other Ovarian Tumors
Although they are rare, teratomas are the next most common ovarian tumor after a GCT. They are also unilateral but are not hormonally active and do not alter the mare’s behavior. The opposite ovary remains active and the mare exhibits normal estrous activity during the physiologic breeding season. A teratoma is a germ cell tumor and may contain cartilage, bone, hair, mucus, and other tissues. The surface of the ovary tends to be sharp and irregular on palpation, and the varying density of the aberrant tissues causes abnormal shadows on the ultrasound image (). Although an ovarian teratoma generally is thought of as being benign, this author has reported on one malignant case that had metastasized to several organs.
Even more rare tumors of the equine ovary include cystadenomas and dysgerminomas. Cystadenomas tend to be benign, whereas dysgerminomas may be malignant. They are both unilateral and hormonally inactive. Thus the contralateral ovary and behavior are normal. The ultrasonographic image of a cystadenoma can resemble that of multiple follicular activity. The same considerations for surgical removal apply as for GCT.